Coordinated Actions of MicroRNAs with other Epigenetic Factors Regulate Skeletal Muscle Development and Adaptation

Abstract

Epigenetics plays a pivotal role in regulating gene expression in development, in response to cellular stress or in disease states, in virtually all cell types. MicroRNAs (miRNAs) are short, non-coding RNA molecules that mediate RNA silencing and regulate gene expression. miRNAs were discovered in 1993 and have been extensively studied ever since. They can be expressed in a tissue-specific manner and play a crucial role in tissue development and many biological processes. miRNAs are responsible for changes in the cell epigenome because of their ability to modulate gene expression post-transcriptionally. Recently, numerous studies have shown that miRNAs and other epigenetic factors can regulate each other or cooperate in regulating several biological processes. On the one hand, the expression of some miRNAs is silenced by DNA methylation, and histone modifications have been demonstrated to modulate miRNA expression in many cell types or disease states. On the other hand, miRNAs can directly target epigenetic factors, such as DNA methyltransferases or histone deacetylases, thus regulating chromatin structure. Moreover, several studies have reported coordinated actions between miRNAs and other epigenetic mechanisms to reinforce the regulation of gene expression. This paper reviews multiple interactions between miRNAs and epigenetic factors in skeletal muscle development and in response to stimuli or disease.

Expression Patterns of Muscle-Specific miR-133b and miR-206 Correlate with Nutritional Status and Sarcopenia

“…The maintenance of muscle homeostasis is finely regulated by the orchestrate action of muscle-specific transcription factors and epigenetic regulators. These include DNA methylation, histone modification, as well as the non-coding microRNAs (miRNAs) [14]. MicroRNAs are small molecules, approximately 21-22 nucleotides in length, able to regulate the expression of their targets by binding to 5 UTR, coding regions or 3 UTR of mRNAs, causing translational inhibition or mRNA degradation [15].…”

A cirkuláris ribonukleinsav és tumorbiológiai jelentősége

“…Míg a TF-ok a gén promóterrégiójának specifikus szekvenciájához kötődve fejtik ki aktiváló vagy csendesítő hatásukat, addig a mi-RNS-ek a citoplazmában az mRNS-ekhez kötődve járulnak hozzá azok transzlációjának gátlásához (degradációjához vagy csendesítéséhez) a 3' le nem fordítódó régióhoz kötődve (UTR: untranslated region) [6]. Az utóbbi évek megfigyelései arra is utalnak, hogy a mi-RNS-ek a sejtmagban is funkcióval bírnak, ahol a géntranszkripció-és hisztonfehérjék modifikációjában írták le szerepüket [7,8]. A miRNS-ek biológiai funkcióinak bizonyítékai ma már bőségesen rendelkezésre állnak.…”

Circulating MIR148A associates with sensitivity to adiponectin levels in human metabolic surgery for weight loss

“…Beyond the genome, epigenetics can directly affect the function of genes, and the underlying mechanism that increases the susceptibility to develop a disease ( 12 , 13 ). The coordinated actions of mRNAs with other epigenetic factors ( 14 ) are thought to be responsible for critical changes in the expression and function of genes. The presence of MIR148A has been associated with DNA hypomethylation caused by sequence complementarity between MIR148A and DNMT1 ( 15 , 16 , 17 ).…”